Signals from the IGF-IR and other members of the IR family contribute to the growth, survival, adhesion, and motility of tumor cells. These signals are initiated through recruitment of adapter proteins including the IRS family and Shc proteins, and are mediated through the PI3-kinase, mitogen activated protein (MAP) kinase and stress-activated protein kinase (SAPK) pathways. Regulation of signaling responses from the IGF-IR involves the actions of regulatory adapter proteins including RACK1 and Grb10 that recruit or sequester cytoplasmic proteins, and the actions of phosphatases including tyrosine PTP-1B, PTEN, and PP2A. This review focuses on the signaling pathways that are activated by the IGF-IR in tumor cells, the mechanisms of regulation of these pathways by adapter proteins and phosphatases, and how modulation of IGF-IR signaling could contribute to cancer progression.

Animals↗

PubMedDate not supplied

Acute coronary syndrome: pharmacotherapy.

Acute coronary syndrome (ACS) refers to the spectrum of cardiac disease, from unstable angina to ST-segment-elevation myocardial infarction. In the emergency medical services (EMS) setting, ACS may be more broadly thought to include patients with chest pain or other symptoms believed to have a cardiac origin who have evidence of ischemia or acute myocardial infarction on a 12-lead electrocardiogram, or symptomatic patients with a previous cardiac event or known cardiac disease. Pharmacologic management of these patients is based on the use of three primary classes of drugs: those that affect clotting, those that establish and maintain hemodynamic control, and those that relieve pain. Many of these agents have been evaluated in large clinical trials for in-hospital use, and a number of ongoing studies are assessing their efficacy in the prehospital setting. The appropriateness of prehospital use of specific agents within each class depends on proper patient selection, the necessity of immediate intervention, ease of use in the field, expertise of EMS personnel, and cost-effectiveness of therapy. This consensus group reviewed agents from all three classes (including aspirin, GPIIb/IIIa inhibitors, unfractionated and low-molecular-weight heparins, fibrinolytics, beta-adrenergic blockers, calcium antagonists, nitrates, and morphine) for their overall indication, applicability to the prehospital setting, and current prehospital use.

Acute Disease↗

PubMedDate not supplied

Intervention by an alcohol health worker in an accident and emergency department.

We have evaluated the effect of brief intervention by an alcohol health worker on alcohol consumption by 202 alcohol misusing patients. For 71 patients where questionnaires were successfully completed, 46 (65%) reported drinking less alcohol at 6 months as opposed to six (8.5%) who reported drinking more. The overall reduction was statistically significant (P < 0.001), with a mean reduction of 43%.

Adult↗

PubMedDate not supplied

Rifampin and pseudomembranous colitis.

Isolates of toxigenic Clostridium difficile, the most frequent cause of antibiotic-associated pseudomembranous colitis, are almost always highly susceptible to rifampin. However, resistant isolates exist and have been associated with colitis in both hamsters and humans given rifampin. Rifampin is rarely implicated in the disease in humans; only six cases have been documented, all in elderly patients receiving treatment for tuberculosis. At least three of these patients had liver disease, and all six had also received one or more other antimicrobial agents. The only isolate of C. difficile from these patients that was studied was resistant to rifampin. The colitis was usually mild and responsive to discontinuation of treatment with rifampin or to oral treatment with vancomycin.

Aged↗